title: Development and characterization of an orodispersible film containing drug nanoparticles.
abstract: In this study, a novel orodispersible film (ODF) containing drug nanoparticles was developed with the goal of transforming drug nanosuspensions into a solid dosage form and enhancing oral bioavailability of drugs with poor water solubility. Nanosuspensions were prepared by high pressure homogenization and then transformed into ODF containing drug nanoparticles by mixing with hydroxypropyl methylcellulose solution containing microcrystalline cellulose, low substituted hydroxypropylcellulose and PEG-400 followed by film casting and drying. Herpetrione, a novel and potent antiviral agent with poor water solubility that extracted from Herpetospermum caudigerum, was chosen as a model drug and studied systematically. The uniformity of dosage units of the preparation was acceptable according to the criteria of Japanese Pharmacopoeia 15. The ODF was disintegrated in water within 30s with reconstituted nanosuspensions particle size of 280 ± 11 nm, which was similar to that of drug nanosuspensions, indicating a good redispersibility of the fast dissolving film. Result of X-ray diffraction showed that HPE in the ODF was in the amorphous state. In the in vitro dissolution test, the ODF containing HPE nanoparticles showed an increased dissolution velocity markedly. In the pharmacokinetics study in rats, compared to HPE coarse suspensions, the ODF containing HPE nanoparticles exhibited significant increase in AUC0-24h, Cmax and decrease in Tmax, MRT. The result revealed that the ODF containing drug nanoparticles may provide a potential opportunity in transforming drug nanosuspensions into a solid dosage form as well as enhancing the dissolution rate and oral bioavailability of poorly water-soluble drugs.
authors.affiliation: 302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing, China; Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Bao-de
authors.initials: BD
authors.lastname: Shen
authors.forename: Cheng-ying
authors.initials: CY
authors.lastname: Shen
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Yuan
authors.forename: Jin-xia
authors.initials: JX
authors.lastname: Bai
authors.forename: Qing-yuan
authors.initials: QY
authors.lastname: Lv
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Dai
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Hai-long
authors.initials: HL
authors.lastname: Yuan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D019540:Area Under Curve; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005663:Furans / Q000008:administration & dosage*; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012996:Solutions; D013535:Suspensions; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000998:Antiviral Agents; D005663:Furans; D012996:Solutions; D013535:Suspensions; C582460:herpetrione; D014867:Water; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002482:Cellulose; D008747:Methylcellulose; C008079:hydroxypropylcellulose
keywords: Film casting; High pressure homogenization; Nanosuspensions; Orodispersible films